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Relationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes.
Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Cerri, Paulo Sérgio; Gil, Cristiane Damas; de Jesus Simões, Manuel.
Afiliación
  • Florencio-Silva R; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Ginecologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, S
  • Sasso GRDS; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil.
  • Sasso-Cerri E; São Paulo State University (UNESP), School of Dentistry, Araraquara - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, Araraquara, SP, Brazil.
  • Cerri PS; São Paulo State University (UNESP), School of Dentistry, Araraquara - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, Araraquara, SP, Brazil.
  • Gil CD; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil.
  • de Jesus Simões M; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Ginecologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, S
Ann Anat ; 257: 152318, 2024 Aug 30.
Article en En | MEDLINE | ID: mdl-39216675
ABSTRACT

BACKGROUND:

Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM.

METHODS:

Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1ß (IL-1ß) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed.

RESULTS:

Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1ß, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1ß, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1ß, and NLRP3, and MMP-9 vs. NFκB.

CONCLUSIONS:

In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Ann Anat Asunto de la revista: ANATOMIA Año: 2024 Tipo del documento: Article Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Ann Anat Asunto de la revista: ANATOMIA Año: 2024 Tipo del documento: Article Pais de publicación: Alemania